Lacosamide

Classification:A

Drug products:Vimpat

ATC code: N03AX18

Substances: lacosamide

Summary

The inter-individual variability in pharmacokinetics is large. Differences have been shown in some studies, with higher exposure and lower elimination in women in than men. However, most of the difference disappear if weight adjustment is performed. No larger analyses of sex differences regarding efficacy or safety have been found.

Additional information

Pharmacokinetics and dosing

A study in healthy volunteers (24 men, 43 women) found women to have higher AUC and Cmax than men. Elderly men and women had higher exposure of lacosamide than their younger counterparts. Without correction for weight and lean body weight young women had 36% higher AUC and 42% higher Cmax than young men. After weight correction, only 3% difference remained in AUC and 13% in Cmax [1]. In a study in patients with focal epilepsy (287 men, 278 women), clearance was higher in men (men 2.06 L/H and women 1.88 L/h) [2]. A Norwegian study based on routine measures of lacosamide (165 men, 179 women) found a pronounced pharmacokinetic variability despite similar doses. Neither differences between men and women nor differences related to age were found [3]. Clinical studies show that patient's sex does not have a clinically significant effect on the plasma concentrations of lacosamide and no sex differentiation in dosing has been recommended by the manufacturer [4].

Effects

The number of men and women included in the RCT of lacosamide as add-on treatment in epilepsy has been similar [5]. A small retrospective study of the effect of lacosamide in children (14 boys, 8 girls) with a mean age of 12.9 years found the proportion of responders to be 75% in girls and 29% in boys. Responders were defined as having a lasting ≥50% reduction of seizures [6].

Adverse effects

The number of men and women included in the RCT of lacosamide as add-on treatment in epilepsy has been similar [5]. Analysis of adverse events and lacosamide concentrations have been published (33 men, 37 women) but no relevant sex analysis on adverse effect was presented [7].

Other information

An observational study in patients with focal epilepsy using lacosamide as an add-on (61 men, 67 women) found the maximal concentration to be higher in women (37±24 µmol/L) than in men (27±13 µmol/L) [11].

A Finnish study of antiepileptic drug utilization in focal refractory epilepsy in adults found 137 patients using lacosamide, 51% women and 49% men. The retention rate was high, 77% (95%CI 68-84%) and similar in men and women [12].

A small study in men (n=11) treated with levetiracetam and carbamazepine found that when the enzyme inducer carbamazepine was exchanged for lacosamide, the men showed favorable changes and more normalized levels in serum profiles of lipids, and reproductive and thyroid hormones [13]. The clinical significance of this is unknown.